糖溶性反应PGAM抑制了Th17的致病性和Th17依赖的自身免疫性
Chao Wang1, Allon Wagner2, Johannes Fessler3
1Biological Sciences Platform, Sunnybrook Research Institute, Toronto, ON M4N 3M5, Canada; Department of Immunology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Cell reports
|June 7, 2025
概括
糖酸盐突变酶 (PGAM) 负面调节致病性T助手17 (Th17) 细胞的分化. 在Th17细胞中抑制PGAM会恶化神经炎症,突出其在促进非致病性表型中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 代谢途径 代谢途径
- 细胞代谢的细胞代谢.
背景情况:
- 葡萄糖代谢极大地影响T细胞的激活和分化.
- 辅助性T17 (Th17) 细胞在免疫反应中起着关键作用,可以表现出致病性或非致病性表型.
研究的目的:
- 为了研究特定的糖溶性反应如何影响Th17细胞的致病性.
- 确定调节Th17细胞致病差异化的关键酶.
主要方法:
- 利用指南针算法从单细胞RNA测序数据推断代谢状态.
- 在Th17细胞中扰乱了糖酸酶突变酶 (PGAM) 活性.
- 评估基因表达特征和致病性标志物.
- 在实验性自身免疫脑膜炎 (EAE) 鼠标模型中评估了Th17细胞功能.
主要成果:
- 指南针算法预测了3-糖酸盐 (3PG) 到2-糖酸盐 (2PG) 的代谢突变和Th17细胞致病性之间的反相关性.
- 扰乱PGAM,催化这种突变的酶,诱导了一种致病性基因表达程序.
- 在EAE模型中,PGAM抑制在Th17细胞中加剧了神经炎症,这表明它在促进非致病性表型方面发挥了作用.
结论:
- PGAM作为病原性Th17细胞分化的负调节剂,与其他糖解酶相反.
- 向PGAM可能为由致病性Th17细胞驱动的炎症和自身免疫疾病提供治疗策略.
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